L32- Hypothalamic and Pituitary Hormones (GH) Flashcards Preview

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Flashcards in L32- Hypothalamic and Pituitary Hormones (GH) Deck (23)
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1

GH:
-most important during (1) age
-directly activates (2) signalling via cell surface receptors
-majority of effects are mediated by (3)

(somatotropin)
1- childhood, adolescence

2- JAK/STAT

3- IGF-1 (insulin like growth factor 1)

2

list the many physiological effects of somatotropin:
-(1) MSK changes
-(2) renal changes
-stimulation of (3) cell development
-antagonizes action of (4)
-develops and increases functions of (5)

1- stimulates longitudinal bone growth inc bone mineral density, inc muscle mass

2- inc GFR

3- preadipocytes --> adipocytes

4- anti-insulin actions (dec glucose utilization, inc lipolysis)

5- immune system

3

GH deficiency:
-(1) causes
-(2) seen in children
-(3) is main blood feature seen in all

1- genetic or damage to pituitary / hypothalamus

2- short stature, adiposity

3- hypoglycemia (unopposed insulin actions)

4

GH deficiency: criteria for Dx

-growth rate <4cm per year
AND
-absence of serum GH response to two GH secretagogues

5

(1) = recombinant GH

(2) = GH analog

1- somatotropin
2- somatrem

6

Somatrem = (1)
Somatotropin = (2)

1- GH analog
2- recombinant GH

7

describe administration of GH (pharmacokinetics)

-active blood levels persist for ~36 hrs

-give SQ x3-7 per wk

8

recombinant GH AEs in children

(somatotropin)
Generally well-tolerated
-scoliosis (rapid growth)
-hypothyroidism

-intracranial HTN is rare
-otitis media, high risk in Turner Pts
-pancreatitis, gynecomastia, nevus growth
-diabetic syndrome with chronic use

9

recombinant GH AEs for adults

-peripheral edema, myalgia, arthralgia (hands/wrists)
-carpal tunnel syndrome

-proliferative retinopathy (rare)

10

recombinant GH contraindications

-cytochrome P450 inducer
-Pts with known malignancy

11

Mecasermin = (1):
-(2) uses / indications, caused by (3)

1- IGF-1 analog (recombinant human IGF-1 and recombinant human IGF-binding protein-3)

2- IGF-1 deficiency (rare)

3- mutations in genes for GH receptor and development of neutralizing Igs to GH

12

Mecasemin = (1): (2) AEs

1- IGF-1 analog (recombinant human IGF-1 and recombinant human IGF-binding protein-3)

2- hypoglycemia (usually eat w/in 20 mins of taking med, before or after)
Rare: intracranial HTN, asymptomatic elevation of liver enxymes

13

GH secreting tumors are more common in (adults/children). If small in size, (2) is the treatment. If too large, (3) is generally the treatment.

1- adults- acromegaly (children gigantism)

2- GH receptor antagonists, somatostatin analogs, dopamine receptor agonists

3- surgery, radiation

14

GH receptor antagonist = _______ (include indication)

Pegvisomant- for small GH producing tumors (adenomas)

15

Somatostatin analog = (1):
-(2) actions
-(3) main indication

1- Octreotide

2- inhibits release of GH, TSH, glucagon, insulin, gastrin

3- small GH producing tumors (adenomas)

16

name the drugs used to treat GH secreting tumors:
-(1) somatostatin analog
-(2) dopamine agonists
-(3) GH receptor antagonists

1- octreotide

2- bromocriptine, cabergoline

3- pegvisomant

17

Octreotide:
-(1) analog with (2) better than (1)
-(3) is special formulation with (4) advantage

1- somatostatin analog

2- 45x more potent at reducing GH, 2x more potent at reducing insulin; 1/2 life ~80min vs 30min

3- octreotide acetate
4- long-acting suspension, given at 4 week intervals

18

Octreotide clinical applications

(somatostatin analog)
-reduces Sxs from hormone secreting tumors: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, nesidioblastosis, watery diarrhea, hypokalemia, achlorhydria syndrome, diabetic diarrhea

-localizing neuroendocrine tumors

-acute control of bleeding from esophageal varices

19

Octreotide AEs

(somatostatin analog)
-n/v/d (steatorrhea), abdominal cramps, flatulence, constipation
-biliary sludge / gallstones (20-30% Pts after 6 mo. use)

-sinus bradycardia (25%, conduction disturbances (10%)
-vitB12 deficiency with long-term use
-pain at injection site is common

20

_____ is main pharmalogical feature of PRL producing adenomas

they retain inhibition by dopamine

21

list the main dopamine agonists; include route of administration, 1/2 life

oral or vaginal inserts
-bromocriptine- ~7hr 1/2 life
-cabergoline- ~65hr 1/2 life

22

describe the uses of bromocriptine / cabergoline

(dopamine agonists)
Hyperprolactinemia: restores ovulation in 70% women with microadenoma, only 30% with macroadenoma

Acromegaly- alone or in addition to surgery, radiation, octreotide therapy

23

Bromocriptine, Cabergoline AEs

(dopamine agonists)
-nausea (more bromo-)
-HAs, lightheadedness, orthostatic hypotension, fatigue

-occasionally psychiatric manifestations

-high doses = cold-induced peripheral digital vasospasm
-chronic high dose = pulmonary infiltrates